Abstract

Background: Structural abnormalities across multiple white matter tracts are recognised in people with early psychosis, consistent with dysconnectivity as a neuropathological account of symptom expression. We applied advanced neuroimaging techniques to characterise microstructural white matter abnormalities for a deeper understanding of the developmental aetiology of psychosis.

Results: Patients with first-episode psychosis had lower regional FA in multiple commissural, corticospinal, and association tracts. These abnormalities predominantly colocalized with regions of reduced neurite density, rather than aberrant fibre bundle arrangement (orientation dispersion index). There was no direct relationship with active symptomatology. FA decreased and orientation dispersion index increased with age in patients, but not controls, suggesting accelerated effects of white matter geometry change.

Conclusions: Deficits in neurite density appear fundamental to abnormalities in white matter integrity in early psychosis. In the first application of NODDI in psychosis, we found that processes compromising axonal fibre number, density, and myelination, rather than processes leading to spatial disruption of fibre organisation, are implicated in the aetiology of the disorder. This accords with a neurodevelopmental origin of aberrant brain-wide structural connectivity predisposing individuals to psychosis.